PubMed Health⌕ Search

Biomedical subjects

Michael J Avram

Publications and source records attributed to Michael J Avram.

At least 19 recordsLinked to original sources
PubMed2007

Circulatory transport and capillary-tissue exchange as determinants of the distribution kinetics of inulin and antipyrine in dog.

A pharmacokinetic model was developed to estimate physiologically meaningful parameters of distribution kinetics from plasma concentration-time data. The model is based on simultaneously measured disposition curves of drug and vascular marker. Employing residence time distribution theory, a recirculatory model with two subsystems, the pulmonary and systemic circulation, was constructed. In addition to intravascular mixing, the axially distributed model of the systemic circulation accounts for transcapillary transport of solutes, quantified by permeability-surface area product (PS) and diffusional equilibration time. Parameters of ICG, inulin, and antipyrine were estimated from disposition data obtained in awake dogs under control conditions and during an isoproterenol infusion or moderate hypovolemia. Results suggest that distribution kinetics is (1) governed by extravascular diffusion and (2) its dependency on cardiac output decreases with increasing diffusional resistance. Hemorrhage decreased the effective PS of inulin. In conclusion, this novel mechanistic model effectively described both the permeability-limited distribution of inulin into interstitial fluid and the flow-limited distribution of antipyrine into total body water and might be useful for other drugs.

Animals↗
PubMed2007

Correlation of the myocardial performance index with conventional echocardiographic indices of systolic and diastolic function: a study in cardiac surgical patients.

BACKGROUND: The aim of this investigation was to compare the myocardial performance index (MPI), a Doppler-derived parameter of global ventricular function, with standard echocardiographic measures of systolic and diastolic function in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: Complete two-dimensional and Doppler examinations were performed on 46 CABG patients after induction of anesthesia (baseline), 15 minutes postcardiopulmonary bypass (CPB), and at the end of the surgical procedure. RESULTS: A strong inverse correlation between MPI and both fractional area change (adjusted r(2)= 0.588-0.802) and ejection fraction (adjusted r(2)= 0.576-0.656, both P < 0.001) of the left ventricle was observed throughout the intraoperative period. Following CPB, a weaker correlation was observed between MPI and overall diastolic heart function classification (adjusted r(2)= 0.224-0.268, P <0.001). Weak, though statistically significant, correlations were observed between MPI and deceleration time (P < 0.05), peak atrial reversal (AR) wave velocity (P < or =0.002), and duration of the AR wave (P < 0.05). CONCLUSION: Our data suggest that the MPI correlates well with standard echocardiographic measures of systolic function and modestly well with overall diastolic heart function classification. The MPI may be a useful, complementary marker of global left ventricular function in patients undergoing CABG surgery.

Aged↗
PubMed2006

Recirculatory pharmacokinetic model of the uptake, distribution, and bioavailability of prochlorperazine administered as a thermally generated aerosol in a single breath to dogs.

A thermal aerosol generation process is capable of delivering pure drug reliably to the alveoli where it is absorbed systemically. Although deep lung absorption of drugs administered as an aerosol has been shown to be rapid, detailed characterization of their absorption and distribution has not been reported. The present study describes the pharmacokinetics of prochlorperazine from the moment of administration as either a rapid intravenous infusion or a thermally generated aerosol and determines the bioavailability of the aerosol by two independent methods. Prochlorperazine disposition was determined in four anesthetized dogs after a 5-s intravenous infusion and after thermally generated aerosol administration in one breath. Venous blood samples were collected frequently from the time of drug administration to 24 h and left ventricular blood samples were drawn more often until 10 min after drug administration. Prochlorperazine disposition after intravenous and aerosol administration was characterized by fitting a recirculatory model to left ventricular and venous drug concentration data simultaneously. Prochlorperazine aerosol administration produced plasma drug concentrations similar to those after rapid intravenous administration of the same nominal dose, with peak left ventricular concentrations achieved in less than 30 s. Plasma concentration profiles of prochlorperazine administered by both routes were well described by the recirculatory model. Bioavailability of the thermally generated aerosol was consistent and averaged more than 80% of emitted dose. Pulmonary administration of a thermally generated drug aerosol in one breath may be a viable alternative to rapid intravenous administration of drugs requiring rapid and predictable production of effective plasma concentrations.

Aerosols↗
PubMed2006

Transit time dispersion in pulmonary and systemic circulation: effects of cardiac output and solute diffusivity.

We present an in vivo method for analyzing the distribution kinetics of physiological markers into their respective distribution volumes utilizing information provided by the relative dispersion of transit times. Arterial concentration-time curves of markers of the vascular space [indocyanine green (ICG)], extracellular fluid (inulin), and total body water (antipyrine) measured in awake dogs under control conditions and during phenylephrine or isoproterenol infusion were analyzed by a recirculatory model to estimate the relative dispersions of transit times across the systemic and pulmonary circulation. The transit time dispersion in the systemic circulation was used to calculate the whole body distribution clearance, and an interpretation is given in terms of a lumped organ model of blood-tissue exchange. As predicted by theory, this relative dispersion increased linearly with cardiac output, with a slope that was inversely related to solute diffusivity. The relative dispersion of the flow-limited indicator antipyrine exceeded that of ICG (as a measure of intravascular mixing) only slightly and was consistent with a diffusional equilibration time in the extravascular space of approximately 10 min, except during phenylephrine infusion, which led to an anomalously high relative dispersion. A change in cardiac output did not alter the heterogeneity of capillary transit times of ICG. The results support the view that the relative dispersions of transit times in the systemic and pulmonary circulation estimated from solute disposition data in vivo are useful measures of whole body distribution kinetics of indicators and endogenous substances. This is the first model that explains the effect of flow and capillary permeability on whole body distribution of solutes without assuming well-mixed compartments.

Adrenergic beta-Agonists↗
PubMed2006

Opioids and cardioprotection: the impact of morphine and fentanyl on recovery of ventricular function after cardiopulmonary bypass.

OBJECTIVES: Experimental studies have shown that opioids protect the myocardium from ischemic injury and that opioid cardioprotection is enhanced by the coadministration of volatile anesthetics. Previous data suggest that morphine produces a more potent cardioprotective effect than fentanyl. The present study investigated the effect of the choice of intraoperative opioid (morphine or fentanyl) on recovery of myocardial function after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized study. SETTING: University hospital. PARTICIPANTS: Forty-six patients undergoing CABG surgery. INTERVENTIONS: Patients were randomly assigned to receive either morphine (40 mg) or fentanyl (1,000 mug) before cardiopulmonary bypass (CPB). Global cardiac function was assessed intraoperatively using the myocardial performance index (MPI), which combines echocardiographic parameters of both systolic and diastolic function. MEASUREMENTS AND MAIN RESULTS: The MPI (median [range]) was increased after CPB in the fentanyl group, indicating a significant worsening of global left ventricular function (0.43 [0.28-0.54] baseline; 0.49 [0.32-0.64] 15 minutes post-CPB; 0.51 [0.36-0.63] end of operation; p < 0.05 post-CPB compared with baseline). The MPI improved in the morphine group after CPB (0.44 [0.32-0.64] baseline; 0.36 [0.24-0.45] 15 minutes post-CPB; 0.34 [0.20-0.46] end of operation; p < 0.05 post-CPB compared with baseline and the fentanyl group). CONCLUSIONS: In patients undergoing CPB, global ventricular function is enhanced by the administration of morphine prior to the ischemic insult of cardioplegic arrest.

Aged↗
PubMed2006

Retrograde autologous priming of the cardiopulmonary bypass circuit: safety and impact on postoperative outcomes.

OBJECTIVES: Retrograde autologous priming (RAP) is a blood conservation technique used to limit the severity of hemodilution during cardiopulmonary bypass and reduce perioperative transfusions. The aim of this investigation was to examine the safety of RAP and to determine the effect of RAP on adverse outcomes after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: University hospital. PARTICIPANTS: Five hundred fifty-nine undergoing cardiopulmonary bypass. INTERVENTIONS: Data were retrospectively collected on 2 cohorts of adult cardiac surgical patients operated on by a single surgeon. In the RAP group (n = 256), outcome data were analyzed on all subjects over a 2-year period during which RAP was used routinely. This group was compared with a similar cohort of patients undergoing cardiopulmonary bypass over a 2-year period immediately before the introduction of RAP into the clinical practice (no-RAP group, n = 287). MEASUREMENTS AND MAIN RESULTS: In-hospital mortality was not significantly different between the RAP group (2.7%) and the no-RAP group (3.8%, p = 0.636). The incidence of postoperative cardiac arrest was significantly less in the RAP group (1 patient) compared to the no-RAP group (9 patients, p = 0.040). There were no differences between the 2 groups in the incidence of several other postoperative complications, including postoperative delirium (1.6% RAP v 3.1% no RAP), heart block (1.6% RAP v 4.2% no RAP), atrial fibrillation (19.1% RAP v 22.7% no RAP), and requiring postoperative ventilation >24 hours (2.7% RAP v 5.2% no RAP). CONCLUSIONS: The authors observed no evidence of any increase in adverse events in the RAP group of this retrospective cohort study, but they did observe a decrease in the incidence of postoperative cardiac arrest in the RAP group. These findings suggest that RAP is a safe technique and may have a beneficial effect on postoperative outcomes.

Adult↗
PubMed2006

Phase I and pharmacokinetic study of docetaxel, irinotecan, and celecoxib in patients with advanced non-small cell lung cancer.

PURPOSE: We studied the toxicities, potential pharmacokinetic interactions, and preliminary antitumor activity of the combination of docetaxel and irinotecan with celecoxib, a selective cyclooxygenase-2 inhibitor. PATIENTS AND METHODS: Eligible patients had advanced non-small lung cancer (NSCLC) with measurable disease, good performance status, and adequate end organ function. Docetaxel and irinotecan were administered intravenously on days 1 and 8, every 21 days, and their doses were escalated on successive patient cohorts at three dose levels: 30/50, 30/60, and 35/60 (doses in mg/m2). Celecoxib was administered at a starting dose of 400 mg orally twice daily without interruption, beginning on day 2 of cycle 1. Pharmacokinetic studies were performed on day 1 of cycle 1 and day 1 of cycle 2. RESULTS: Seventeen patients with advanced NSCLC were enrolled and collectively received 78 cycles of therapy. Diarrhea was the most common toxicity; it was noted in 13 patients (76%). Dose-limiting toxicities occurred at dose level 1 (myocardial infarction in a patient with multiple coronary artery disease risk factors) and dose level 3 (grade 4 neutropenia with fatal urosepsis). Other major toxicities were: grade 3 neutropenia (2 patients); grade 3/4 diarrhea (3/1); grade 3 nausea (2); grade 2 rash (1); and grade 3 pneumonitis (1). The maximum tolerated dose was at dose level 3, i.e., docetaxel 35 mg/m2 and irinotecan 60 mg/m2 on days 1 and 8, plus celecoxib 400 mg twice daily, repeated every 21 days. Five of 15 evaluable patients achieved an objective response. The pharmacokinetics of docetaxel were not altered by celecoxib. However, we observed an 18% increase in the average elimination clearance of irinotecan coincident with the addition of celecoxib. CONCLUSIONS: The addition of celecoxib to docetaxel and irinotecan was generally well tolerated but unpredictable fatal toxicity occurred. Diarrhea was the most common toxicity. Antitumor activity was promising. The alteration of irinotecan pharmacokinetic parameters observed may not be clinically relevant.

Adult↗
PubMed2006

Pharmacokinetics of midazolam, propofol, and fentanyl transfer to human breast milk.

BACKGROUND AND OBJECTIVES: Lactating women undergoing operations requiring general anesthesia are advised to pump and discard their milk for 24 hours after the procedure. Data on anesthetic drug transfer into breast milk are limited. This study determined the pharmacokinetics of midazolam, propofol, and fentanyl transfer into milk to provide caregivers with data regarding the safety of breast milk after administration of these drugs. METHODS: Five lactating women participated in this study after providing institutionally approved written informed consent. Patients underwent premedication with midazolam before induction of anesthesia with propofol and fentanyl. Anesthesia was maintained with a potent volatile anesthetic. Milk and blood were collected before drug administration. Milk was collected 5, 7, 9, 11, and 24 hours after drug administration. Venous blood was collected at intervals up to 7 hours. Plasma and milk midazolam, propofol, and fentanyl concentrations were measured by HPLC with tandem mass spectrometric or fluorescence detection. The pharmacokinetics of drug transfer into milk was modeled with plasma pharmacokinetics. RESULTS: Plasma midazolam, propofol, and fentanyl pharmacokinetics were consistent with reports of others. In 24 hours of milk collection, averages of 0.005% (range, 0.002%-0.013%) of the maternal midazolam dose, 0.027% (0.004%-0.082%) of the propofol dose, and 0.033% (0.006%-0.073%) of the fentanyl dose were collected in milk, representing averages of 0.009%, 0.025%, and 0.039% of the respective elimination clearances. CONCLUSION: The amount of midazolam, propofol, and fentanyl excreted into milk within 24 hours of induction of anesthesia provides insufficient justification for interrupting breast-feeding.

Adult↗
PubMed2006

Retrograde blood flow in the brachial and axillary arteries during routine radial arterial catheter flushing.

BACKGROUND: Flushing of radial arterial catheters may be associated with retrograde embolization of air or thrombus into the cerebral circulation. For embolization into the central circulation to occur, sufficient pressure must be generated during the flushing process to reverse antegrade blood flow in the arterial blood vessels of the upper extremity. This ultrasound study was designed to examine whether routine radial catheter flushing practices produce retrograde blood flow patterns in the brachial and proximal axillary arteries. METHODS: Duplex ultrasound examinations of the brachial and axillary arteries were conducted in 100 surgical patients to quantify direction and velocity of blood flow during catheter flushing. After obtaining Doppler spectral images of brachial and axillary arterial flow patterns, manual flushing was performed by injecting 10 ml flush solution using a syringe at a rate reflecting standard clinical practices. The flow-regulating device on the pressurized (300 mmHg) arterial flushing-sampling system was then opened for 10 s to deliver a rapid bolus of fluid (flush valve opening). RESULTS: The rate of manual flush solution injection through the radial arterial catheter was related to the probability of retrograde flow in the axillary artery (P < 0.001). Reversed arterial flow was noted in the majority of subjects (33 of 51) at a manual flush rate of less than 9 s and in no subjects (0 of 48) at a rate 9 s or greater. Retrograde flow was observed less frequently during flush valve opening (2 of 99 patients; P < 0.001 vs. manual flushing). CONCLUSIONS: Rapid manual flushing of radial arterial catheters at rates faster than 1 ml/s produces retrograde flow in the proximal axillary artery.

Adult↗
PubMed2005

Residual paralysis at the time of tracheal extubation.

Respiratory and pharyngeal muscle function are impaired during minimal neuromuscular blockade. Tracheal extubation in the presence of residual paresis may contribute to adverse respiratory events. In this investigation, we assessed the incidence and severity of residual neuromuscular block at the time of tracheal extubation. One-hundred-twenty patients presenting for gynecologic or general surgical procedures were enrolled. Neuromuscular blockade was maintained with rocuronium (visual train-of-four [TOF] count of 2) and all subjects were reversed with neostigmine at a TOF count of 2-4. TOF ratios were quantified using acceleromyography immediately before tracheal extubation, after clinicians had determined that complete neuromuscular recovery had occurred using standard clinical criteria (5-s head lift or hand grip, eye opening on command, acceptable negative inspiratory force or vital capacity breath values) and peripheral nerve stimulation (no evidence of fade with TOF or tetanic stimulation). TOF ratios were measured again on arrival to the postanesthesia care unit. Immediately before tracheal extubation, the mean TOF ratio was 0.67 +/- 0.2; among the 120 patients, 70 (58%) had a TOF ratio <0.7 and 105 (88%) had a TOF ratio <0.9. Significantly fewer patients had TOF ratios <0.7 (9 subjects, 8%) and <0.9 (38 subjects, 32%) in the postanesthesia care unit compared with the operating room (P < 0.001). Our results suggest that complete recovery from neuromuscular blockade is rarely present at the time of tracheal extubation.

Adolescent↗
PubMed2004

Beta-adrenergic blockade affects initial drug distribution due to decreased cardiac output and altered blood flow distribution.

Beta-adrenergic receptor blockers decrease intravenous anesthetic dose requirements. The present study determined the effect of propranolol on indocyanine green and antipyrine disposition from the moment of rapid intravenous injection. Anti-pyrine is a physiological marker that distributes to a volume as large as total body water in a blood flow-dependent manner and is a pharmacokinetic surrogate for many lipophilic drugs, including intravenous anesthetics. Antipyrine and indocyanine green disposition were determined twice in five healthy adult males in this Institutional Review Board-approved study, once during propranolol infusion. After rapid indocyanine green and antipyrine injection, arterial blood samples were collected frequently for 2 min and less frequently thereafter. Plasma indocyanine green and antipyrine concentrations were measured by high-performance liquid chromatography. Indocyanine green and antipyrine disposition were characterized, using SAAM II, by a recirculatory pharmacokinetic model that describes drug disposition from the moment of injection. Parameters were compared using the paired t test. The disposition of indocyanine green demonstrated that propranolol decreased cardiac output at the expense of the fast peripheral (nonsplanchnic) intravascular circuit. The area under the antipyrine concentration versus time relationship was doubled for at least the first 3 min after injection due to both decreased cardiac output and maintenance of nondistributive blood flow at the expense of a two-thirds reduction of blood flow (intercompartmental clearance) to the rapidly equilibrating (fast, splanchnic) tissue volume. The increase in antipyrine area under the curve due to propranolol-induced alteration of initial antipyrine disposition could explain decreased intravenous anesthetic dose requirements in the presence of beta-adrenergic receptor blockade.

Adrenergic beta-Antagonists↗
PubMed2004

Retrograde air embolization during routine radial artery catheter flushing in adult cardiac surgical patients: an ultrasound study.

BACKGROUND: Rapid flushing of radial artery catheters may result in retrograde embolization of air into the cerebral circulation. This study examined the incidence of central air embolization during and after flushing of an arterial pressure monitoring system. METHODS: One hundred adult patients undergoing cardiac surgical procedures were enrolled in this study. Ten ml of saline and blood were withdrawn into a syringe in the arterial flushing-sampling pressure system and then readministered to the patient through a 20-gauge radial artery catheter over 3-12 s. The right carotid artery, left carotid artery, and aortic arch were visualized using ultrasound imaging techniques during three manual flushes of the system. The left and right common carotid arteries were examined for the presence of macrobubbles or microbubbles using a linear array ultrasound transducer. The aortic arch was imaged using transesophageal echocardiography to detect retrograde air emboli. The severity of air embolization was quantified using a modification of an established grading system. RESULTS: A total of 298 ultrasound studies in 100 patients were recorded and analyzed after radial artery catheter flushing. Two aortic arch images were not obtained because of an inability to place the probe. Most clinicians (54%) returned flush solution to patients at near-maximal injection rates (2-3 ml per second). No air emboli (macrobubbles or microbubbles) were detected in the carotid arteries or aortic arch of any subject. CONCLUSION: Retrograde air embolization is a rare event after routine radial artery catheter flushing in adult patients with stable hemodynamic conditions.

Aged↗
PubMed2004

Postanesthesia care unit recovery times and neuromuscular blocking drugs: a prospective study of orthopedic surgical patients randomized to receive pancuronium or rocuronium.

UNLABELLED: In this study, we examined the effect of choice of neuromuscular blocking drug (NMBD) (pancuronium versus rocuronium) on postoperative recovery times and associated adverse outcomes in patients undergoing orthopedic surgical procedures. Seventy patients were randomly allocated to a pancuronium or rocuronium group. On arrival to the postanesthesia care unit (PACU) and again 30 min later, train-of-four ratios were quantified by using acceleromyography. Immediately after acceleromyographic measurements, patients were assessed for signs and symptoms of residual paresis. During the PACU admission, episodes of hypoxemia, nausea, and vomiting were recorded. The time required for patients to meet discharge criteria and the time of actual PACU discharge were noted. Forty percent of patients in the pancuronium group had train-of-four ratios <0.7 on arrival to the PACU, compared with only 5.9% of subjects in the rocuronium group (P < 0.001). Patients in the pancuronium group were more likely to experience symptoms of muscle weakness (blurry vision and generalized weakness; P < 0.001) and hypoxemia (10 patients in the rocuronium group versus 21 patients in the pancuronium group; P = 0.015) during the PACU admission. Significant delays in meeting PACU discharge criteria (50 min [45-60 min] versus 30 min [25-40 min]) and achieving actual discharge (70 min [60-90 min] versus 57.5 min [45-61 min]) were observed when the pancuronium group was compared with the rocuronium group (P < 0.001). In conclusion, our study indicates that PACU recovery times may be prolonged when long-acting NMBDs are used in surgical patients. IMPLICATIONS: Clinical recovery may be delayed in surgical patients administered long-acting neuromuscular blocking drugs. During the postanesthesia care unit admission, patients randomized to receive pancuronium (versus rocuronium) were more likely to exhibit symptoms of muscle weakness, develop hypoxemia, and require more time to meet discharge criteria.

Adult↗
PubMed2004

The failure of retrograde autologous priming of the cardiopulmonary bypass circuit to reduce blood use after cardiac surgical procedures.

UNLABELLED: Hemodilution during cardiopulmonary bypass (CPB) is a primary risk factor for blood transfusion in cardiac surgical patients. Priming of the CPB circuit with the patients' own blood (retrograde autologous priming, RAP) is a technique used to limit hemodilution and reduce transfusion requirements. We designed this study to examine the impact of RAP on perioperative blood product use. Using a retrospective cohort study design, the medical records of all patients undergoing CPB (excluding circulatory arrest cases) by a single surgeon were examined. Data were collected over a 24-mo period when RAP was routinely used as a blood conservation strategy (RAP group, n = 257). This group was compared with a cohort of patients during the 24 mo immediately preceding the introduction of RAP into clinical practice (no RAP group, n = 288). A small, statistically insignificant reduction in the percentage of patients receiving packed red blood cells was observed in the RAP group (44% versus 51% no RAP, P = 0.083). No differences were found between the groups in the number of units of packed red blood cells, platelets, or fresh frozen plasma transfused throughout the perioperative period. These results suggest that overall, RAP does not offer a clinically important benefit as a blood conservation technique. IMPLICATIONS: Priming of the cardiopulmonary bypass circuit with the patients' own blood (retrograde autologous priming) resulted in insignificant reductions in blood use in a large, unselected group of patients undergoing cardiac surgical procedures.

Adult↗
PubMed2003

Declining proportion of publications by American authors in major anesthesiology journals.

A decline in the proportion of articles published by American authors in medical journals has been reported. We therefore sought to determine whether the contributions of authors from the United States to the three leading anesthesia journals changed between the years 1980 to 2000. The journals Pain, Anesthesiology, and Anesthesia & Analgesia were selected for evaluation on the basis of their respective impact factors. All clinical studies and basic science studies published in the years 1980, 1985, 1990, 1995, and 2000 were evaluated. The country of origin of the lead author of each article was determined by two of the investigators. chi(2) Tests and least squares linear regression analyses were used to determine associations between the source of publication (United States or abroad) and year of publication. The proportion of American publications in the leading anesthesia specialty journals was found to be decreasing over the period 1980-2000 because of an increase in the rate of publication from abroad that is disproportionate to the increase in the total number of publications in the journals over that time. The reasons for changes in anesthesia-related publications by American authors were not established by this study. The authors speculate that multiple factors are involved, including an increased emphasis on clinical care over research because of economic constraints, American publication in journals other than the leading specialty journals, and the increased quality of submissions from abroad.

Anesthesiology↗
PubMed2003

Using front-end kinetics to optimize target-controlled drug infusions.

BACKGROUND: The mode of drug administration, blood sampling schedule, and sampling site affect the pharmacokinetic model derived. The present study tested the hypothesis that three-compartment pharmacokinetic model parameters derived from arterial drug concentrations obtained after rapid intravenous administration can be used to design a target-controlled drug infusion (TCI) that deviates minimally from the target. METHODS: Arterial thiopental concentration data obtained from the moment of injection in a previous study of five dogs were used. Three three-compartment models were constructed, one based on early concentrations classically obtained at 1, 2, and 3 min; another using all concentrations obtained beginning with the thiopental recirculation peak; and the last with the initial distribution volume (VC) fixed to the sum of VC and the nondistributive volume of the recirculatory model from the earlier study. Using these models, TCIs were designed that would maintain 20 mug/ml thiopental concentrations in VC for 60 min if simulated with the models used in their design. Drug concentrations resulting from these TCIs were then simulated using recirculatory model kinetics, and prediction errors were evaluated. RESULTS: Models with VCs estimated from intermittent or frequent early blood concentrations overestimated not only VC but also the volume and clearance of the rapidly equilibrating tissues, and their TCIs significantly overshot the target. With VC fixed to recirculatory model parameters, drug distribution was described in a manner consistent with that of the recirculatory model, and the TCI deviated minimally from the target. A similar three-compartment model was derived from data obtained from a simulation of a 2-min infusion using recirculatory kinetic parameters. CONCLUSIONS: Because three-compartment models based on drug concentration histories obtained after rapid intravenous administration do not characterize VC accurately, TCIs based on them produce concentrations exceeding the target. A model capable of producing TCIs deviating minimally from the target can be derived from data obtained during and after a brief drug infusion.

Anesthetics, Intravenous↗
PubMed2003

Recovery of neuromuscular function after cardiac surgery: pancuronium versus rocuronium.

UNLABELLED: The use of pancuronium in fast-track cardiac surgical patients may be associated with delays in clinical recovery. Our objective in this study was to evaluate the incidence and severity of residual neuromuscular blockade after cardiac surgery in patients randomized to receive either pancuronium (0.08-0.1 mg/kg) or rocuronium (0.6-0.8 mg/kg). Eighty-two patients undergoing cardiopulmonary bypass were randomized to a pancuronium (n = 41) or rocuronium (n = 41) group. Intraoperative and postoperative management was standardized. In the intensive care unit, train-of-four (TOF) ratios were measured each hour until weaning off ventilatory support was initiated. Neuromuscular blockade was not reversed. After tracheal extubation, patients were examined for signs and symptoms of residual paresis. When weaning of ventilatory support was initiated, significant neuromuscular blockade was present in the pancuronium subjects (TOF ratio: median, 0.14; range, 0.00-1.11) compared with the rocuronium subjects (TOF ratio: median, 0.99; range, 0.87-1.21) (P < 0.05). Patients in the rocuronium group were more likely to be free of signs and symptoms of residual paresis than patients in the pancuronium group. Our findings suggest that the use of longer-acting muscle relaxants in cardiac surgical patients is associated not only with impaired neuromuscular recovery, but also with signs and symptoms of residual muscle weakness in the early postoperative period. IMPLICATIONS: The use of long-acting muscle relaxants in fast-track cardiac surgical patients is associated with significant residual neuromuscular block in the intensive care unit, including signs and symptoms of residual paresis.

Adult↗